34例HIV患者新生隐球菌感染分子流行病学及临床特点分析

摘要/Abstract

摘要：

目的了解HIV患者新生隐球菌感染的分子流行病学及其临床特点，为HIV患者新生隐球菌感染的预防和治疗提供依据。方法收集首次分离自HIV患者的新生隐球菌34株，回顾性分析患者一般资料；VITEK MS质谱仪进行菌种鉴定，ATB Fungus3测定新生隐球菌对5种抗真菌药物的MIC值；利用PCR对特异性引物扩增，确定变种和交配型；多位点序列分型（MLST）对菌株进行分子遗传学分析。结果 34株新生隐球菌绝大部分分离自中年男性，且主要来自脑脊液（73.5%）标本；初次脑脊液压力平均为（27.26±11.52）mmH₂O，CD4细胞计数中位数28 cells/μL（3~163 cells/μL），脑脊液白细胞中位计数32（2~110）×10⁶/L，蛋白质定量中位数为362 mg/L（160~2 730 mg/L），葡萄糖含量中位数为2.28 mmol/L（1.50~5.98 mmol/L）；所有菌株对5种抗真菌药均敏感，且所有菌株均为Aα、VNⅠ型；MLST分析共检出3种ST型，ST5（n=32）、ST32（n=1）和ST186（n=1）。结论近两年本地区HIV合并新生隐球菌感染主要以中年男性多见，常规实验室检查缺乏特异性，对临床常用抗真菌药物耐药性不强，ST5是其感染的主要克隆系。

关键词: 新生隐球菌, HIV, 流行病学, 多序列位点分型

Abstract:

Objective To analyze the molecular epidemiology and clinical characteristics of cryptococcosis occurred in HIV-infected patients, and to provide evidence for the prevention and treatment of cryptococcosis. Methods A total of 34 Cryptococcus neoformans strains isolated from HIV-infected patients were collected and the general data of patients were investigated retrospectively. The isolates were first identified based on the matrix-assisted laser desorption/ionization time-of flight mass spectrometry (MALDI-TOF MS), the MICs of the five kinds of antifungal drugs were carried out according to ATB Fungus3. PCR with specific primers were used to identify variants and mating types. The clonal relatedness was characterized by multilocus sequence typing (MLST) analysis. Results Most Cryptococcus neoformans strains were isolated from middle-aged men and mainly came from cerebrospinal fluid (73.5%). Cerebrospinal fluid pressure was (27.26±11.52) mmH₂O on average,median CD4 T-cell count was 28 cells/μL (3~163 cells/μL), median CSF WBC count was 32 (2~110)×10⁶/L, the median protein was 362 mg/L (160~2 730 mg/L), median glucose 2.28 mmol/L (1.50~5.98 mmol/L). All strains were sensitive to five kinds of antifungal drugs and were identified as serotype A, mating type α and molecular type VNⅠ. MLST analysis divided the 34 isolates into two sequence types (STs), including ST5 (n=32), ST32 (n=1) and ST186 (n=1). Conclusion In recent two years, cryptococcosis occurred in HIV-infected patients were more common in middle-aged men. The laboratory tests lacked specificity. The resistance of Cryptococcus neoformans isolates from HIV-infected patients was not serious, ST5 is the main clonal.

Key words: Cryptococcus neoformans, HIV, molecular epidemiology, MLST

中图分类号:

R379.5

陈艳慧, 俞凤, 边泽源, 洪建明, 钟桥石, 杭亚平, 张楠, 胡龙华. 34例HIV患者新生隐球菌感染分子流行病学及临床特点分析[J]. 中国真菌学杂志, 2018, 13(3): 152-157.

CHEN Yan-hui, YU Feng, BIAN Ze-yuan, HONG Jian-ming, ZHONG Qiao-shi, HANG Ya-ping, ZHANG Nan, HU Long-hua. Molecular epidemiology and clinical characteristics of 34 cases of cryptococcal infection in HIV patients[J]. Chinese Journal of Mycology, 2018, 13(3): 152-157.

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